8 Fascinating Practicals You Will Do as a Medical Student
Robert Cronshaw describes eight fascinating practicals you will do in your medical degree and explains the science behind them.
Being a medical student isn’t all about reading textbooks or sitting through long lectures; a significant proportion of your time will be spent doing practicals.
These are a great chance to consolidate what you have learned in relation to them. They also tend to be very enjoyable illustrations of what you have learned. If you’re a practically-minded person, they will put everything into a useful context, often involving yourself as part of the experiment! Practicals are also a better reflection of the kind of thing you may end up doing in your future career as a doctor than poring over textbooks ever could be.
1. Blood typing (and other agglutination experiments)
Your blood type is defined by specific specific carbohydrate chains on the surface of red blood cells (Type A and B). People who are type A express one, type B the other, AB both and type O neither. If you do not express a certain carbohydrate chain your immune cells will recognise this ‘antigen’ as foreign and mount an immune response when it is detected, meaning that if a type A patient were injected with type B red blood cells they would react to it.
Therefore it is very important to determine the blood type of both a donor and a recipient before a blood transfusion takes place. One way this can be done is by an agglutination experiment. Agglutination is a process that can happen to red blood cells when they are cross-linked together in the bottom of a small well or test tube. Normally if they are left undisturbed they will simply settle to the bottom and form a small blob there. If, however, there are antibodies present which will react to an antigen expressed on the red blood cells (such as the type A or B antigens) they will cross-link many red blood cells together to form a fine net or mesh across the bottom. This then provides us with a mechanism with which to determine your blood group: add anti-A antibody to one well, anti-B to a second and control solution to a third. Add a small amount of your blood to each well and observe whether the red blood cells have agglutinated or simply settled to the bottom. If they have agglutinated for A only you are type A, for B only type B, for both type AB and for neither type O.
Agglutination can also be used for the detection of flu virus. Flu virus expresses haemagglutination units, so if red blood cells are added to a suspension of flu virus, haemagglutination will be observed. If a person is infected with a specific strain of flu virus they will express anti flu antibodies which block the haemagglutination action of that strain. Therefore when their serum is added to the haemagglutination well the flu will no longer be able to bind the red blood cells together (as it is being blocked by antibody) and instead the cells will sediment to the bottom of the well. This is part of a wider family of virus diagnostics called virus neutralisation (where serum from an infected individual will block the viral action in vitro due to the presence of antibodies).
2. Measuring blood pressure
Sometimes some of the practicals you do can seem very far removed from the reality of being a doctor so it can be very enjoyable to do an exceptionally relevant one such as this. Many people are familiar with the procedure of taking a blood pressure reading: inflating a pressure cuff, placing a stethoscope further down the arm on the artery and then slowly deflating the pressure cuff. But what is actually going on here?
When the pressure cuff is initially inflated it is inflated to a pressure above that of both systolic and diastolic blood pressure, meaning that the artery on the arm is forced completely closed. The cuff’s pressure is then slowly reduced while the doctor listens to the artery further along the arm. When the pressure in the cuff reaches a value roughly equal to the systolic pressure in the artery a sound can be heard through the stethoscope: this is the Korotkoff sound. It is actually the sound of blood spurting through and inducing vibration in the artery as the blood pressure momentarily passes above that of the cuff and forces blood through the artery, although the pressure read off from the cuff is actually approximately a 10mmHg underestimate. The pressure at which this sound first starts to appear is called the systolic pressure as it occurs during the contraction of the heart, or systole. As the pressure in the cuff continues to drop the artery remains open for most of the cardiac cycle, only being forced closed by the cuff near the lowest levels of diastole.
Eventually the Korotkoff sounds will disappear as blood will no longer be effectively spurting through and this is accepted as the diastolic blood pressure, although it is actually an 8mmHg overestimate. This is an overestimate because, in order to generate a Korotkoff sound, the artery must be occluded for a significant percentage of the cardiac cycle, so the pressure in the cuff must be higher than the bottom of diastole.
3. Saccadic eye movements
Saccades are small but very rapid movements made by the eyes in order to change what we are looking at. While the centre of the eye (the fovea) is capable of a very high resolution (100MP) most of the eye is not, so it is important to be able to shift our gaze onto targets of interest. In the experiment the subject has their head fixed in place and a helmet placed on their head with a camera attached that is capable of detecting eye movements using IR light. They are then asked to perform a number of tasks, which analyse information such as the speed of eye movement during the saccade and also the delay between a stimulus and a saccade being performed.
The basic setup consists of a bar set up at a fixed distance from the subject with three lights on it: one in the middle and two at the edges, in the subject’s outer vision. Initially the central light is lit and the subject focuses on it. When a switch is pressed the central light turns off and one of the peripheral lights switches on. As a result the subject switches their attention to it and performs a saccade. The speed of movement can be measured using the IR detector; the maximum speed of a human saccade is around 900 degrees per second. The delay between stimulus and saccade (latency) is actually remarkably variable, even from saccade to saccade in the same subject. It has been suggested that this is related to an advantageous evolutionary adaption of behaving in an unpredictable fashion so that predators and prey would not be able to anticipate our actions easily.
4. Electrocardiogram (ECG)
In order to understand the principles of an ECG it must first be understood how cells in the heart transfer the signal to contract to adjacent cells. Normally cardiac cells are polarised: they have an uneven electrical potential across their cell membranes. This is due to the distribution of charged ions inside and outside of the cell, as well as how permeable the cell is to different types of ion. When cardiac cells are contracting they are depolarised, the movement of positive ions into the cell stops the inside of the cell being so negatively charged. As different parts of the heart are contracting at different moments some parts of the heart will be depolarised, while others are still polarised. This means that there will be an electrical potential in a certain direction across the heart. The ECG leads are then capable of detecting this potential, but only a certain component. If you have an electrode on both wrists only the horizontal component of a diagonal depolarisation could be measured. The output generated is a series of peaks and troughs, varying slightly depending on where you attach the electrodes and thus what components you have.
The P wave here represents atrial depolarisation/contraction, the QRS complex represents the rapid depolarisation of the ventricles and the T wave is the repolarisation of the ventricles. Many cardiac defects can be recognised by someone skilled at interpreting an ECG but an easy one to identify is long QT syndrome. This is a genetic disorder which results in delayed repolarisation of the ventricles and therefore a longer QT interval on the ECG. This can cause ventricular arrhythmia and therefore death if unnoticed.
5. Mitochondrial activity
Mitochondria are the real power producers of any eukaryotic cell and are relevant in many diseases, including cancer, as they are part of the ‘apoptotic’ pathway (cell suicide) which is often blocked in cancers so that the tumour cells can continue to proliferate despite inhibitory signals. Mitochondria work by taking a chemical energy source and producing ATP, an energy source easily utilised by the cell. This is achieved by using the chemical input to create a gradient of H+ ions across the mitochondrial membrane. These are linked to ATP production when they flow back into the cell. One way mitochondrial activity can be measured is via the P:O ratio — the ratio between ATP produced and oxygen consumed. A specific electrode is used to detect the levels of oxygen in solution and a limited amount of ADP (which is subsequently converted to ATP) is added. The mitochondria are then left until all the ADP is consumed and the amount of oxygen consumed to achieve this is measured.
If the mitochondria are dysfunctional, the P:O ratio will be changed, so that more oxygen is used without providing extra ATP. This can be due to mutated mitochondria that allow H+ ions to leak across without producing ATP, but can also be induced by a mitochondrial uncoupler such as 2,4-DNP. Normally H+ ions can only flow through the mitochondrial membrane in such a way that they generate ATP, but an uncoupler offers them an alternative pathway where they travel bound to the uncoupling agent, thereby dissipating the energy instead of using it to drive the synthesis of ATP.
6. Polymerase Chain Reaction
PCR is a key component of modern medicine, being used in a diagnostic context with increasing frequency. The basic concept is amplifying a single stretch of DNA enough times that it is present in a large enough concentration to be detectable. This works using a DNA polymerase, an enzyme which will generate a matching strand of DNA to an unpaired strand in solution, given the correct resources. One of these is a suitable primer: an artificial short strand of DNA that will bind to the start of the DNA sequence you are interested in and act as a starting point for the polymerase.
Two primers are used: one to mark the start of the interesting sequence and one to mark the end. Each of these will provide a starting point for a DNA polymerase on the two opposing strands and as such DNA outside these primed regions will not be amplified.
This process can be used as a diagnostic tool by designing primer sequences which will only bind to a particular stretch of DNA, such as a genetic mutation or pathogen DNA. Therefore only in these cases will the PCR be effective and generate a lot of DNA, which can then be detected using a polyacrylamide gel.
7. Ischaemic Nerve Block
Put simply, this experiment cuts off the blood supply to your arm (ischaemia) and as a result stops sensory information from your arm being passed to the brain. This is achieved by inflating a pressure cuff (the same device that is used to measure blood pressure) above the subject’s systolic blood pressure at the level of the upper arm, thereby preventing blood flowing beyond it. The experimental subject will then sit like this for around 40 minutes, having their different senses and motor function tested until they are lost, with the order of the loss of different senses/motor function recorded. Of course this seems a little dangerous — aren’t nerve cells exceptionally sensitive to ischemia? (Brain cells will suffer damage from lack of oxygen after about 4 minutes).
The reason this experiment is actually very safe is that the motor and sensory nerve cell bodies are located in or next to the spinal cord respectively, and it is these which are vulnerable to oxygen deprivation. The reason that the nerve fibres stop functioning is that the ischaemia deprives the arm of the resources (blood and glucose) that are required to keep the nerve trunk in a state where it can generate action potentials and pass information to and from the arm. Motor control and touch are the first functions lost, as these rely on large, myelinated A-alpha and A-beta fibres (very vulnerable to lack of oxygen). Pain and temperature involve small myelinated A-delta fibres, which are slightly less susceptible. Warmth and slow pain sensation travels through unmyelinated C fibres which are least susceptible to anoxia and thus these sensations will be preserved the longest.
Interestingly, as function is lost, the experimental subject has the sensation that the arm is no longer theirs and is simply a ‘thing’ attached to them.
8. Testing reflexes
Reflex testing is a key clinical skill and the science behind it can be investigated in a practical class. Using electrodes attached to the muscle that carries out the reflex the time delay between stimulation and reaction can be measured. This is achieved by using a specific tendon hammer which triggers the start of a recording of the electrode output. Interestingly, the magnitude of the reflex can be increased with the Jendrassik manouevre: linking the hands together and pulling outwards against each other. This will boost the response of the patellar reflex (where the leg kicks forward) and will increase the response even more if it is applied rapidly just as the tendon hammer is about to hit. The mechanism of this is still poorly understood, but it has been suggested that performing this action weakens central inhibition from the brain by providing an alternative focus. Recent studies, however, have shown this to be unlikely, and it is still an active area of debate. While this manoeuvre has been used for many years in clinical examination it is still poorly understood.
This goes to show that there is still a great deal for science to learn and as a medical student you will be brought to the forefront of current knowledge and shown how we are trying to push things further. I have given a very brief description of a very limited selection of the practicals you do as a medical student, but I hope I have provided enough to really spark off excitement and interest in being a medical student and potentially provide a starting point for further reading in an area which really appeals to you.